Project Summary: Core 5, Optical Instrumentation Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. This multi-component research project aims to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. Our projects have been designed to take full advantage of new optics-based technologies developed in the BRAIN Initiative. It is imperative that we continue to innovate and upgrade our instrumentation and methods as the cutting edge of the field moves forward. The Optical Instrumentation Core will develop, implement, and support the optical microscopes and other optics-based instrumentation used in our projects to ensure that they represent the best of the new technologies. To do so, we will leverage the technical and engineering expertise in Princeton?s Bezos Center for Neural Circuit Dynamics and recruit additional staff devoted to constructing and maintaining our state-of-the-art instruments. Our projects depend on the latest technology for two- and three-photon calcium imaging at cellular resolution, laser-based optogenetic perturbation systems combined with simultaneous imaging, and novel forms of widefield microscopy. Some of this instrumentation is based on recent innovations in the labs of our PIs. In other cases, we will collaborate with colleagues at other institutions who have developed innovative new methods. Creating an Optical Instrumentation Core will address the problem that much of the technical work required to innovate and maintain these instruments has shifted to students and postdocs, because it has exceeded the capacity of existing staff. This division of labor is a problem for four reasons: (1) lab personnel often do not have sufficient time or expertise to produce the best possible results, (2) the diffusion of responsibility leads people to duplicate one another?s efforts, (3) researchers spend their time on technical work at the expense of doing science, and (4) expertise can be lost as students and postdocs move on. For all these reasons, we propose to standardize this function across projects to improve quality control and efficiency. Centralizing the design, construction, maintenance, and support of these instruments will increase the efficiency and rigor of our microscopy experiments, while freeing lab personnel to focus on designing experiments and collecting data.